U.S. patent application number 10/316849 was filed with the patent office on 2003-10-30 for muscle-strengthening drugs and anti-inflammatory drugs.
This patent application is currently assigned to DAICHO KIKAKU INCORPORATED COMPANY. Invention is credited to Daicho, Takao, Kosuge, Masaki, Miura, Oto, Nukaya, Haruo, Ochiai, Akio, Okada, Kenkichi, Tsuji, Kuniro.
Application Number | 20030203057 10/316849 |
Document ID | / |
Family ID | 27347974 |
Filed Date | 2003-10-30 |
United States Patent
Application |
20030203057 |
Kind Code |
A1 |
Okada, Kenkichi ; et
al. |
October 30, 2003 |
Muscle-strengthening drugs and anti-inflammatory drugs
Abstract
An object of the present invention is to provide a
pharmaceutical agent or composition useful as a
muscle-strengthening drug, an anti-inflammatory drug, an
antiasthmatic, an antidiarrheal, an antidepressant, or a drug for
the treatment of secondary diseases following cerebral infarction,
motor paralysis, diminution of vision, hepatitis, inflammatory
intestinal syndrome, functional enteropathy, functional
cardiopathy, functional hepatopathy, functional nephropathy,
dementia, climacteric symptoms, senile dementia and/or Alzheimer
disease, and a dermatological agent or composition suitable for
skin applications, which can treat or prevent muscle weakening and
inflammation, in particular arthritis, by its muscle-strengthening
and/or anti-inflammatory actions, said agent or composition
comprising isoflavone and/or isoflavone glycoside in combination
with a pungent substance, a bitter substance or a sour substance,
and cholic acid, and/or scymnol and/or a scymnol ester. The present
invention relates to an agent or composition usuful as a
muscle-strengthening drug, an anti-inflammatory drug, an
antiasthmatic, an antidiarrheal, an antidepressant, or a drug for
the treatment of secondary diseases following cerebral infarction,
motor paralysis, diminution of vision, hepatitis, inflammatory
intestinal syndrome, functional enteropathy, functional
cardiopathy, functional hepatopathy, functional nephropathy,
dementia, climacteric symptoms, senile dementia and/or Alzheimer
disease, and/or an agent or composition to be applied to the skin,
said agent or composition comprising isoflavone and/or isoflavone
glycoside in combination with a pungent substance, a bitter
substance or a sour substance, and cholic acid, and/or scymnol
and/or a scymnol ester.
Inventors: |
Okada, Kenkichi;
(Shinagawa-ku, JP) ; Ochiai, Akio; (Shimizu-shi,
JP) ; Kosuge, Masaki; (Shizuoka-shi, JP) ;
Daicho, Takao; (Shida-gun, JP) ; Tsuji, Kuniro;
(Shizuoka-shi, JP) ; Nukaya, Haruo; (Shimizu-shi,
JP) ; Miura, Oto; (Musashino-shi, JP) |
Correspondence
Address: |
OLIFF & BERRIDGE, PLC
P.O. BOX 19928
ALEXANDRIA
VA
22320
US
|
Assignee: |
DAICHO KIKAKU INCORPORATED
COMPANY
Shida-gun
JP
|
Family ID: |
27347974 |
Appl. No.: |
10/316849 |
Filed: |
December 12, 2002 |
Current U.S.
Class: |
424/750 ;
424/764; 514/171; 514/27; 514/456 |
Current CPC
Class: |
A61P 27/02 20180101;
A61K 36/36 20130101; A61K 36/734 20130101; A61P 25/24 20180101;
A61K 35/413 20130101; A61K 36/31 20130101; A61K 36/258 20130101;
A61K 45/06 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 2300/00 20130101; A61K 2300/00 20130101; A61K
2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00 20130101;
A61K 2300/00 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101; A61K 36/725 20130101; A61P 9/02 20180101; A61P 9/10
20180101; A61P 21/00 20180101; A61P 25/28 20180101; A61K 35/60
20130101; A61K 36/344 20130101; A61K 36/484 20130101; A61K 31/366
20130101; A61K 2300/00 20130101; A61K 36/23 20130101; A61K 36/344
20130101; A61K 36/725 20130101; A61K 36/8969 20130101; A61P 25/02
20180101; A61K 36/23 20130101; A61K 36/258 20130101; A61K 36/36
20130101; A61P 1/16 20180101; A61K 36/481 20130101; A61K 36/484
20130101; A61K 36/481 20130101; A61K 36/8969 20130101; A61K 36/31
20130101; A61K 36/899 20130101; A61P 13/12 20180101; A61P 1/00
20180101; A61K 36/734 20130101; A61P 39/00 20180101; A61K 31/366
20130101; A61P 1/12 20180101; A61K 36/284 20130101; A61K 36/8945
20130101; A61K 36/8945 20130101; A61K 36/284 20130101; A61P 9/00
20180101; A61P 11/06 20180101; A61P 29/00 20180101; A61K 36/899
20130101; A61P 1/04 20180101 |
Class at
Publication: |
424/750 ;
424/764; 514/27; 514/171; 514/456 |
International
Class: |
A61K 035/78; A61K
031/7048; A61K 031/57; A61K 031/353 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 18, 2001 |
JP |
2001-384849 |
Oct 7, 2002 |
JP |
2002-293899 |
Oct 18, 2002 |
JP |
2002-303877 |
Claims
What is claimed is:
1. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides; and/or at
least one or more members selected from the group consisting of
pungent substances, bitter substances and sour substances; and/or
at least one or more members selected from the group consisting of
scymnol and scymnol esters.
2. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides, and cholic
acid, or at least one or more members selected from the group
consisting of scymnol and scymnol esters.
3. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides; and at least
one or more members selected from the group consisting of pungent
substances, bitter substances and sour substances; and cholic acid,
or at least one or more members selected from the group consisting
of scymnol and scymnol esters.
4. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides; and cholic
acid.
5. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides; and at least
one or more members selected from the group consisting of pungent
substances, bitter substances and sour substances; and cholic
acid.
6. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides, and at least
one or more members selected from the group consisting of scymnol
and scymnol esters.
7. An agent or composition which is used as a muscle-strengthening
drug, an anti-inflammatory drug, an antiasthmatic, an
antidiarrheal, an antidepressant, or a drug for the treatment of
secondary diseases following cerebral infarction, motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and/or an agent
or composition to be applied to the skin, said agent or composition
comprising at least one or more members selected from the group
consisting of isoflavones and isoflavone glycosides; at least one
or more members selected from the group consisting of pungent
substances, bitter substances and sour substances; and at least one
or more members selected from the group consisting of scymnol and
scymnol esters.
8. The agent or composition used as a muscle-strengthening drug, an
anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to claim 1, wherein the
isoflavone is a soybean isoflavone, and the isoflavone glycoside is
a soybean isoflavone glycoside.
9. The agent or composition used as a muscle-strengthening drug, an
anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to claim 1 or 2, wherein the
pungent substance, the bitter substance or the sour substance is
selected from foods.
10. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to any of claims 1 to 3, which
comprises a pungent substance.
11. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to any of claims 1 to 4,
wherein the pungent substance is curcumin.
12. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to any of claims 1 to 5, which
is in admixture with a vitamin.
13. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to any of claims 1 to 6, which
is in admixture with at least one or more members selected from
galenical preparations (herbal drugs or crude drugs).
14. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to claim 7, wherein the
galenical preparation has the property of exerting a "FUSEI"
action.
15. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to claim 7 or 8, wherein the
galenical preparation is one or more members selected from the
group consisting of Ginseng (Panax Ginseng or Ginseng Radix),
Codonopsitis Radix, Psuodostellariae Radix, American Ginseng,
Astragali Radix, Atractylodis Rhizoma, Dioscoreae Rhizome,
Glycyrrhia (Glycyrrhizae Radix), Jujube Fruit (Zizyphi Fructus,
Zizyphus vulgaris), Dulcium (malt sugar derived from Oryza seed),
Polygonati Rhizoma, and Codonopsis lanceolata Benth. et Hock. fil.
("SHIYOUJIN" in Japanese).
16. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to claim 7 or 8, wherein the
galenical preparation is one or more members selected from the
group consisting of Crataegi Fructus, Massa Medicate Fermentat,
Raphani Semen, Fructus Hordei Germinatus, Fructus Oryzae Germinatus
("KOKUGA" in Japanese; Oryza sativa L.), Galli Stomachichum Corium,
and Asa Foetida.
17. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to any of claims 1 to 10, which
is in admixture with inosic acid.
18. The agent or composition used as a muscle-strengthening drug,
an anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction, motor paralysis, diminution of
vision, hepatitis, inflammatory intestinal syndrome, functional
enteropathy, functional cardiopathy, functional hepatopathy,
functional nephropathy, dementia, climacteric symptoms, senile
dementia and/or Alzheimer disease, and/or an agent or composition
to be applied to the skin according to any of claims 1 to 11, which
is in admixture with an odd-numbered fatty acid.
19. The agent or composition used as an agent or composition to be
applied to the skin according to claim 14, wherein said
dermatological agent or composition have one or more actions
selected from the group consisting of skin beautifying actions,
therapeutic actions against atopic dermatitis, various types of
dermatitis, dermatomycosis, verrucosis, pigmentation, vulgar
psoriasis, senile xeroderma, senile keratoma, and skin injuries,
and hair-restoring, peptic juice secretion promoting, perspiration
promoting, lapactic, and diuretic actions.
Description
TECHNICAL FIELD
[0001] The present invention relates to a novel agent or
composition for use as a muscle-strengthening drug, an
anti-inflammatory drug, an antiasthmatic, an antidiarrheal, an
antidepressant, or a drug for the treatment of secondary diseases
following cerebral infarction (human stroke sequelae, secondary
stroke damages or sequelae of brain infarction), motor paralysis,
diminution of vision, hepatitis, inflammatory intestinal syndrome,
functional enteropathy, functional cardiopathy, functional
hepatopathy, functional nephropathy, dementia, climacteric
symptoms, senile dementia and/or Alzheimer disease, and to an agent
or composition to be applied to the skin.
BACKGROUND OF THE INVENTION
[0002] Serotonin and noradrenaline referred to as brain hormones
control satisfaction of the will, and in turn, spiritual
satisfaction. In response to satisfaction of the will, voluntary
muscles are activated by adrenaline, an adrenal medullary hormone,
secreted from adrenal medulla and chromaffin cells on nerve
muscles.
[0003] Serotonin, noradrenaline and adrenaline are also referred to
as biogenic monoamines, and are oxidatively decomposed by an enzyme
called monoamine oxidase within as long as 3 hours or reabsorbed
into nerve tissues and so forth, resulting in the extinction of
most effects of secreted monoamines.
[0004] This is an ingenious body mechanism that prevents fatigue
produced by the long time action of monoamines.
[0005] "KI" (in Japanese; vital energy) refers to all the functions
of the human body. Such body's functions are generically classified
into 2 types. One function is controlled by autonomic nerves, which
are found in various organs, hormone secretions and blood vessels.
The other one works for voluntary muscles which act according to
commands released from brain thought functions and thought
patterns.
[0006] It has previously been pointed out that "KI", as represented
by "HOKI" (in Japanese; complementing energy) and "RIKI" (in
Japanese; circulating energy) in Chinese medicine, indicates only
the former functions controlled by autonomic nerves. The commands
for "which functions will be activated" and "how they will be
exerted" are released from the medulla oblongata located at the
lower part of the brain. Considering that "HOKIYAKU" (in Japanese;
drug for complementing "KI") activates all functions controlled by
autonomic nerves, instead of only activating certain organs and
tissues, it is likely that the target point on which the "HOKIYAKU"
acts may be medulla oblongata (a source of commands) rather than
each organ or tissue. That is, it is concluded that the actions of
"HOKIYAKU" are for enhancing and facilitating the emission and
transmission of commands from the medulla oblongata.
[0007] I have found that the "HOKIYAKU" localizes body blood to
various organs. This might be aimed at achieving such a blood
localization via, as a result of the blood vessel-dilating and
constricting action (one of the important actions of medulla
oblongata), not only dilating blood vessels directed to the
autonomic nervous control system but also constricting blood
vessels directed to the brain and brain-controlled organs whereby
more nutrient elements will be delivered to required parts as a
secondary action of the "HOKIYAKU".
[0008] Further, the onset of depressive syndrome (depression) is
caused by retention of a depressive condition when deprived of
satisfaction of will and spirit due to a decrease in the secretory
capability of biogenic monoamines, whereby the spirit is, on
occasion, extremely lowered leading to strong suicidal
tendencies.
[0009] Until now, for treatment of depression, passive nosotropic
therapy has been carried out in which either pharmaceutical drugs
which inhibit an action of monoamine oxidase or pharmaceutical
drugs which prevent reabsorption of such monoamines are
administered so that the concentration of, as a result of decrease
in the secretory capability, reduced monoamines would be maintained
and an extreme decrease in spirit would be prevented.
[0010] However, this therapy is not a fundamental therapy the aim
of which is to eliminate the cause of depression, that is, to cure
the decreased secretory ability of biogenic monoamines. Thus, it is
a therapy in expectation of only naturally recovering the secretion
capacity of monoamines over a long period of therapy.
[0011] Natural recovery is still a therapy with drawbacks, i.e.,
not only the secretory ability of monoamines is further decreased
due to the continued presence of monoamines, but also physical
strength is readily lowered due to fatigue caused by
adrenaline-mediated excess burning of sugars and lipids.
[0012] It is known in the art that monosaccharides such as glucose
and galactose can moisten the skin. However, such monosaccharides
are applied by dermal application, hence are readily removed from
the skin upon rubbing or washing. It is a problem that such
monosaccharides should always be applied.
[0013] Proctoptosia, and pains in legs, lumbar regions and arms
have occurred with aging. These have been considered to be due only
to hematogenous disorders at the respective local sites or
resultant inflammation. However, regular dosing of drug products
alone which are assumed to be sufficiently capable of eliminating
hematogenous disorders has been insufficient in ameliorating such
conditions.
[0014] These disorders are attributed to insufficient communication
of the brain commands to the local sites. Hematogenous disorders
and the occurrence of inflammation are problems caused by abnormal
motions of muscles due to the incomplete communication of brain
commands.
SUMMARY OF THE INVENTION
[0015] For instance, although all muscle disorders are not ascribed
to insufficient brain communication, it seems that the majority of
such disorders are elicited by insufficient communication of brain
commands. In particular, it has been found that muscle disorders
such as backaches and pains in limbs attributable to aging are
easily eliminated by curcumin and others which ameliorate the
communication of brain commands.
[0016] The present invention has been made to develop
pharmaceutical drugs and compositions based on this novel medical
theory. An object of the present invention is to provide very
effective pharmaceutical drugs and therapeutic compositions having
a muscle-strengthening, antiinflammatory, anti-cerebral infarction
sequela, anti-motor paralysis, antiasthmatic, anti-vision
diminution, antihepatitis, anti-inflammatory intestinal syndrome,
anti-functional enteropahy, and/or anti-dementia activity.
[0017] In former times, depression was a rare disease. However, the
onset rate of depression has recently increased worldwide, and it
is said that one in 150 individuals is a depressive patient in the
Tokyo Metropolitan Area.
[0018] Recently, an interesting opinion has been published
concerning the causes for increases in the occurrence of depressive
symptoms. Such a theory is as follows:
[0019] That is, there has been no war crisis worldwide except in
some troubled regions. In addition, social order has been well
maintained resulting in reducing opportunities for encountering
contingent accidents.
[0020] Thus, there has been almost no need for the human body to
gird itself and enhance the spirit for such dangers.
[0021] Therefore, the need for secretion of biogenic amines has
also remarkably decreased, whereby the secretory capability has
degenerated with the result that persons would be apt to develop
depression.
[0022] If this theory is correct, when secretion of biogenic
monoamines is artificially stimulated, for example using a
secretomotory means once a day, the onset of depression may be
prevented, the capability of secreting biogenic monoamines may be
recovered even in patients whose secretion capability of biogenic
monoamines is lowered, and the patient may recover from
depression.
[0023] The present invention has been made to develop
pharmaceutical drugs and compositions based on such novel medical
theory. An object of the present invention is to provide
pharmaceutical compositions and therapeutic drugs very effective in
the treatment of depression, climacteric disturbance, senile
dementia and/or Alzheimer's disease.
[0024] A further object of the invention is to provide
dermatological agents and compositions, in particular
dermatological agents and compositions for external use, which do
not directly act on the skin but releases a monosaccharide in vivo
after once absorbed into the body and which thus heal a skin
injury, prevent skin deterioration or weakening, or restore healthy
skin.
[0025] The present invention relates to a muscle-strengthening drug
or anti-inflammatory drug-containing muscle strengthening drug
which comprises isoflavone and/or an isoflavone glycoside, and/or a
pungent, bitter or sour substance, and/or cholic acid, and/or
scymnol and/or a scymnol ester.
[0026] The term "muscle-strengthening drug" used herein refers to
an agent acting for reducing muscle fatigue, or increasing muscle
strength, for instance. The term "anti-inflammatory drug" used
herein refers to an agent for the treatment of inflammation, in
particular a therapeutic or prophylactic agent for arthritis,
neuralgia or rheumatism, among others.
[0027] The present invention relates to a pharmaceutical agent or
composition useful as an antiasthmatic, an antidiarrheal, an
antidepressant, a drug for the treatment of secondary diseases
following cerebral infarction, or a drug for the treatment of motor
paralysis, diminution of vision, hepatitis, inflammatory intestinal
syndrome, functional enteropathy, functional cardiopathy,
functional hepatopathy, functional nephropathy, dementia,
climacteric symptoms, senile dementia and/or Alzheimer disease, and
to an agent or composition to be applied to the skin.
[0028] The drug for inflammatory intestinal syndrome as used herein
includes agents for Crohn disease and ulcerative colitis. The
anti-functional enteropathy, anti-functional cardiopathy,
anti-functional hepatopathy, anti-functional nephropathy and/or
antidiarrheal drug as used herein includes anti-irritable bowel
syndrome agents.
[0029] The antiasthmatic, antidiarrheal, antidepressant, drugs for
the treatment of secondary diseases following cerebral infarction,
motor paralysis, diminution of vision, hepatitis, inflammatory
intestinal syndrome, functional enteropathy, functional
cardiopathy, functional hepatopathy, functional nephropathy,
dementia, climacteric symptoms, senile dementia and/or Alzheimer
disease, and agents or compositions to be applied to the skin as
used herein, refer to drugs, agents or compositions/preparations
for the prophylaxis and/or treatment of a disease.
DETAILED DESCRIPTION OF THE INVENTION
[0030] In accordance with the present invention, it is preferable
that the pharmaceutical product (or drug) contains a pungent
substance, a bitter substance, and/or a sour substance. It is more
preferable that the pharmaceutical product is in admixture with one
or more members selected from the group consisting of isoflavones
and isoflavone glycosides. The particularly preferable isoflavone
includes soybean isoflavones comprised in soybean. The particularly
preferable isoflavone glycoside includes soybean isoflavone
glycosides comprised in soybean.
[0031] When isoflavone or isoflavone glycoside is administered, it
is desirable that the pharmaceutical product is in admixture with
one or more members selected from the group consisting of cholic
acid, scymnol and scymnol esters.
[0032] The daily dose of isoflavone and isoflavone glycoside is
preferably 1 to 500 mg, more preferably 5 to 200 mg, and most
preferably 10 to 100 mg.
[0033] A most preferable pharmaceutical product comprises at least
a pungent substance therein.
[0034] The pungent substance as used herein includes preferably
curcumin 1
[0035] (isolated from Curcumae Rhisoma (root of Curcuma longa L.)),
capsaicine 2
[0036] (isolated from fruit of Capsicum annuum L.), piperine 3
[0037] (isolated from black peper (fruit of Piper nigrum L.)),
zingerone 4
[0038] (isolated from ginger root (Zingiber officinale Roscoe)),
(6)-shogaol 5
[0039] (isolated from ginger root), (6)-gingerol 6
[0040] (isolated from ginger root), etc. Among them, curcumin is
most preferable.
[0041] The bitter substance as used herein includes preferably
swertiamarin, gentiopicrin, loganin, etc.
[0042] The sour substance as used herein includes preferably citric
acid, lactic acid, etc.
[0043] The daily dose of the pungent substance is preferably 1 to
1000 mg, more preferably 5 to 300 mg, and most preferably 10 to 70
mg. When it is administered alone, its daily dose is preferably 100
to 800 mg, and most preferably 300 to 500 mg. When it is
administered in combination with "KAMPO" pharmaceutical
preparations or drugs ("KAMPO", Japan's traditional herbal
medicine) having the efficacy of "FUSEI" (as pronounced in
Japanese: aid for keeping the body normal), such as JUZEN-TAIHO-TO
(as pronounced in Japanese), its daily dose is preferably 100 to
200 mg.
[0044] The daily dose of the pungent substance is preferably 1 to
1000 mg, more preferably 10 to 300 mg, and most preferably 20 to 70
mg. When it is administered alone, its daily dose is preferably 100
to 800 mg, and most preferably 300 to 500 mg. When it is
administered in combination with "KAMPO" pharmaceutical
preparations or drugs having the efficacy of "FUSEI", such as
JUZEN-TAIHO-TO (as pronounced in Japanese), its daily dose is
preferably 100 to 200 mg.
[0045] The daily dose of cholic acid is preferably 1 to 1000 mg,
more preferably 2 to 300 mg, and most preferably 10 to 100 mg. The
daily dose of scymnol and scymnol esters is preferably 0.1 to 100
mg, more preferably 0.1 to 50 mg, and most preferably 0.3 to 10
mg.
[0046] In the case of a preparation to be applied to the skin, it
preferably contains a monosaccharide.
[0047] The monosaccharide is preferably glucose or galactose, and
galactose is more preferred.
[0048] The sugar may be a sugar or a sugar acyl ester, and an acyl
ester is preferred.
[0049] The acyl is preferably a fatty acid acyl, and one to all
alcohol moieties may be esterified by an alcohol.
[0050] The content of galactose is preferably 0.1% to 30%, more
preferably 1% to 5%.
[0051] The daily dose of galactose is preferably 0.5 to 500 mg,
more preferably 1 to 100 mg.
[0052] The content of acetylgalactose is preferably 0.1% to 30%,
more preferably 1% to 5%.
[0053] The daily dose of acetylgalactose is preferably 0.5 to 500
mg, more preferably 1 to 100 mg.
[0054] It is also allowable that the pharmaceutical product is in
admixture with other ingredients including not only generic
pharmaceutical drugs but also vitamins, anibiotics, anti-cancer
drugs, heme Fe, prune extracts (Prunus Domestica fruit extracts),
crude drugs (herbal and animal drugs, or galenical preparations;
"SHOUYAKU" as pronounced in Japanese), and the like. The "SHOUYAKU"
includes preferably those having the efficacy of "FUSEI", for
example those capable of activating or stimulating the functions of
organs, glands and blood vessels, all controlled by autonomic
nerves, those capable of aiding digestion, and others.
[0055] The galenical preparations (or crude drugs) of 10 or more
kinds have been known as those capable of activating or stimulating
the functions of organs, glands and blood vessels, all controlled
by autonomic nerves. Examples of such galenical preparations are
ginseng (Ginseng Radix, Panax Ginseng), etc. Some of active
elements have been revealed for not only ginseng but also such
galenical preparations.
[0056] Accordingly, such active elements can be preferably admixed
therewith. The admixture of such active elements will lead to
achievement of activating body-functions.
[0057] The particularly preferable galenical preparation include
Ginseng (Panax Ginseng or Ginseng Radix), Codonopsitis Radix,
Psuodostellariae Radix, American Ginseng, Astragali Radix,
Attractylodis Rhizoma, Dioscoreae Rhizoma, Glycyrrhia (Glycyrrhizae
Radix), Jujube Fruit (Zizyphi Fructus, Zizyphus vulgaris), Dulcium
(malt sugar derived from Oryza seed), Polygonati Rhizoma,
Codonopsis lanceolata Benth. et Hock. fil. ("SHIYOUJIN" in
Japanese; Oryza sativa L.), etc.
[0058] Galenical preparations capable of aiding digestion can be
preferably admixed therewith. The particularly preferable galenical
preparations capable of aiding digestion include Crataegi Fructus,
Massa Medicata Fermentat, Raphani Semen, Fructus Hordei
Germiniatus, Fructus Oryzae Germinatus ("KOKUGA" in Japanese; Oryza
sativa L.), Galli Stomachichum Corium, Asa Foetida, etc.
[0059] In the case of dermal preparations, galenical preparations
capable of producing a monosaccharide having a body fluid producing
activity (so-called "TSUEKI SAYOU" as pronounced in Japanese) or an
antianemic or blood activating activity (so-called "HOKETSU
KAKKETSU SAYOU" as pronounced in Japanese) is preferably added.
[0060] The galenical preparation having body fluid producing
activity includes Hoelen (Poria, "BUKURYO" in Japanese; Poria cocus
WOLF (Pachyma hoelen RUMPHIUS)), "SEKIBUKURYO" (in Japanese; pale
red portion of Poria cocus), "BUKUSHIN" (in Japanese; particular
grade of Poria cocus), "BUKURYOHI" (in Japanese; cortical portion
of Poria cocus), etc. The galenical preparation having antianemic
or blood-activating activity includes Cnidii Rhizoma ("SENKYU in
Japanese; Cnidium officinale MAKINO), Salviae Militiorrhiziae Radix
("TANJIN" in Japanese; Salvia miltiorrhiza BUNGE"), Mucunae Caulis
(Mucuna birdwoodiana, "KEIKETTO" in Japanese; Mucuna birdwoodiana
TUTCHER, stem of Millettia reticulata), "MOUTOUSEI" (in Japanese;
root of Ilex pubescens), among others.
[0061] Scymnol and/or scymnol esters are comprised in biles of
shark. Scymnol has the following formula: 7
[0062] Sodium scymnol sulfate has the following formula: 8
[0063] Other materials as used herein include isoflavones and
isoflavone glycosides.
[0064] For the pharmaceutical products, the active elements
contained in soybean are several species of isoflavone glycosides
including daidzin, glycitin, genistin, etc. and aglycons thereof,
i.e., several species of isoflavones including daidzein, glycitein,
genistein, etc.
[0065] The soybean is a starting material for producing soybean
oil. There is a great demand for soybean oil. Therefore, large
amounts of soybean oil are manufactured together with large amounts
of by-products, soybean cakes. Although part of such soybean cakes
are employed as sources for preparing soybean proteins, etc. which
are starting materials for food products, the soybean cake is
mainly used for a fertilizer or feed for livestock and its price is
therefore extremely low. The soybean cakes which are almost
industrial wastes can be used as starting materials to produce
inexpensively soybean isoflavones and soybean isoflavone glycosides
with high purity.
[0066] Preferably, inosic acid is added to the agent or composition
of the invention.
[0067] Preferably, a fatty acid having an odd number of carbon
atoms ("odd-numbered fatty acid") is added to the agent or
composition of the invention.
[0068] Preferred as the odd-numbered fatty acid are tridecanoic
acid, pentadecanoic acid, heptadecanoic acid and nonadecanoic acid.
Among them, pentadecanoic acid and heptadecanoic acid are more
preferred.
[0069] The dosage form of the pharmaceutical agents or composition
for use as a muscle-strengthening drug, an anti-inflammatory drug,
an antiasthmatic, an antidiarrheal, an antidepressant, or a drug
for the treatment of secondary diseases following cerebral
infarction, of motor paralysis, diminution of vision, hepatitis,
inflammatory intestinal syndrome, functional enteropathy,
functional cardiopathy, functional hepatopathy, functional
nephropathy, dementia, climacteric symptoms, senile dementia and/or
Alzheimer disease, and the agents or compositions to be applied to
the skin according to the invention is not particularly limited but
may be administered, for example, in the form of such preparations
for internal administration or oral route, as tablets, powders,
solid preparations or solutions, suppositories or injectable
solutions.
[0070] An excipient such as lactose or starch, a vegetable oil or
the like may also be used.
[0071] The dermatological agent or composition according to the
invention may be administered in the form of a preparation suitable
for external use, and the dosage form thereof is not particularly
limited but preferably used in the form of a cream, emulsion,
solution or ointment.
[0072] The ingredients to be used in the products may be ordinary
ones used in conventional creams, emulsions, solutions, or
ointments.
EXAMPLES
[0073] Described below are examples of the present invention which
are provided for illustrative purposes.
[0074] Soybean isoflavones and soybean isoflavone glycosides as
used in examples are set to be 40% in purity. Cholic acid as used
in examples is set to be 90% in purity except for pure cholic
acid.
Example 1
Powders
[0075]
1 Curcumin 30 mg Scymnol 1 mg Soybean isoflavone 125 mg Lactose 800
mg Cornstarch qs Magnesium stearate 10 mg Total 2000 mg (1 g per
container (powder paper), twice a day)
[0076] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended to afford powders in the
same fashion as above.
Example 2
Granules
[0077]
2 Curcumin 30 mg Sodium scymnol sulfate 1 mg Soybean isoflavone 125
mg Lactose 1500 mg Cornstarch qs Magnesium stearate 10 mg Total
2000 mg (1 g per container (powder paper), twice a day)
[0078] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was granulated to afford granules in
the same fashion as above.
Example 3
Tablets
[0079]
3 Curcumin 30 mg Sodium scymnol sulfate 1 mg Soybean isoflavone 125
mg Crystalline cellulose qs Lactose 140 mg Magnesium stearate 6 mg
Talc 3 mg Total 1120 mg (280 mg per tablet, 2 tablets per dose,
twice a day)
[0080] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was compressed to afford tablets in
the same fashion as above.
Example 4
Tablets
[0081]
4 Curcumin 25 mg Scymnol 1 mg Soybean isoflavone 250 mg Ginseng
powder 2000 mg Lactose 886 mg Crystalline cellulose qs
Carboxymethylcellulose calcium 320 mg Hydroxypropylcellulose 558 mg
CARPLEX 30 mg Magnesium stearate 55 mg Total 5600 mg (280 mg per
tablet, 5 tablets per dose, twice a day)
[0082] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was compressed to afford tablets in
the same fashion as above.
Example 5
Hard Capsules
[0083]
5 Curcumin 30 mg Scymnol 1 mg Soybean isoflavone 125 mg Lactose 218
mg Cornstarch qs Magnesium stearate 6 mg Total 1150 mg (for 4 #1
capsules, 2 capsules per dose, twice a day)
[0084] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended and packed to afford hard
capsules in the same fashion as above.
Example 6
Soft Capsules
[0085]
6 Curcumin 25 mg Sodium scymnol sulfate 1 mg Soybean isoflavone 125
mg Cod liver oil 80 mg Tocopherol acetate 5 mg Ginseng extract 200
mg Yellow beeswax 55 mg Edible oil qs Total 1200 mg (4 capsules a
day)
[0086] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended and packed to afford soft
capsules in the same fashion as above.
Example 7
Drink
[0087]
7 Curcumin 30 mg Sodium scymnol sulfate 1 mg Soybean isoflavone 125
mg Korean ginseng extract 10 mg Rehmanniae Radix extract 10 mg
(Rehmannia glutinosa Liboschitz var. purpurea Makino) Royal jelly
100 mg Thiamin nitrate 10 mg Riboflavin sodium phosphate 5 mg
Pyridoxine hydrochloride 10 mg Anhydrous caffeine 50 mg Ethanol 1.2
mL Ethyl parahydroxybenzoate 4 mg Purified water qs Total 50
mL/bottle
[0088] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was mixed to afford drinks in the same
fashion as above.
Example 8
Preparations Admixed With Vitamin, Hard Capsules
[0089]
8 Curcumin 25 mg Sodium scymnol sulfate 1 mg Soybean isoflavone 125
mg Thiamin hydrochloride 25 mg Pyridoxine hydrochloride 10 mg
Riboflavin 10 mg Cyanocobalamin 12 mg Nicotinamide 20 mg Calcium
pantothenate 20 mg Ascorbic acid 60 mg L-cysteine 10 mg Lactose 263
mg Magnesium stearate 6 mg Cornstarch qs Total 1150 mg (2 capsules
per dose, twice a day)
[0090] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended and packed to afford hard
capsules in the same fashion as above.
Example 9
Injections
[0091]
9 Curcumin 30 mg Sodium scymnol sulfate 1 mg Pure soybean
isoflavone 20 mg Glucose 500 mg
[0092] The mix was adjusted with 10% sodium hydroxide as a pH
regulator to pH 7. Next, distilled water for injection was added to
the mix to make the total volume 5 ml. The resultant mix was
dispensed into each ampule which was then melt-sealed, and
sterilized.
[0093] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended to afford injections in
the same fashion as above.
Example 10
Powders
[0094]
10 Curcumin 30 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Lactose 2700 mg Cornstarch qs Light anhydrous silicic acid 5
mg Magnesium stearate 10 mg Total 4000 mg (2 g per container
(powder paper), twice a day)
[0095] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended to afford powders in
the same fashion as above.
Example 11
Granules
[0096]
11 Curcumin 25 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Lactose 2700 mg Cornstarch qs Crystalline cellulose 300 mg
Light anhydrous silicic acid 5 mg Magnesium stearate 10 mg Total
4000 mg (2 g per container (powder paper), twice a day)
[0097] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was granulated to afford granules
in the same fashion as above.
Example 12
Spherical Granules
[0098]
12 Curcumin 30 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Lactose 515 mg Cornstarch qs "KAN-BAI-KO" (in Japanese) 500
mg (Prunus mume fruit powder) Crystalline cellulose 400 mg Total
2000 mg (1 g per container (powder paper), twice a day)
[0099] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was granulated to afford spherical
granules in the same fashion as above.
Example 13
Tablets
[0100]
13 Curcumin 30 mg Cholic acid 140 mg Soybean isoflavone glycoside
280 mg Lactose 4000 mg Carboxymethylcellulose calcium 320 mg
Hydroxypropylcellulose 74 mg Crystalline cellulose qs CARPLEX 30 mg
Magnesium stearate 10 mg Total 5484 mg (280 mg per tablet, 5
tablets per dose, twice a day)
[0101] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was compressed to afford tablets
in the same fashion as above.
Example 14
Hard Capsules
[0102]
14 Curcumin 25 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Cornstarch qs Magnesium stearate 9 mg Total 1153 mg (#1
capsule, 4 capsules a day)
[0103] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended and packed to afford
hard capsules in the same fashion as above.
Example 15
Soft Capsules
[0104]
15 Curcumin 30 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Yellow beeswax 55 mg Edible oil qs Total 1200 mg (4 capsules
for a daily dose)
[0105] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended and packed to afford
soft capsules in the same fashion as above.
Example 16
Injections
[0106]
16 Curcumin 25 mg Pure cholic acid 20 mg Pure soybean isoflavone
glycoside 20 mg Glucose 1000 mg Sodium carbonate (pH regulator)
qs
[0107] Distilled water for injection was added to the mix until the
total volume reached 5 ml.
[0108] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended to afford injections
in the same fashion as above.
Example 17
Drink
[0109]
17 Curcumin 30 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Korean ginseng extract 1500 mg Euphoria longan extract 100
mg Schizandrae Fructus fluidextract 300 mg (fruit of Schizandra
chinensis Baill.) Royal jelly 150 mg Riboflavin sodium phosphate 10
mg Ethanol 1.2 ml Parahydroxybenzoic acid 4 mg Purified water qs
Total 50 ml
[0110] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was mixed to afford drinks in the
same fashion as above.
Example 18
Granules
[0111]
18 Curcumin 25 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Thiamin hydrochloride 10 mg Pyridoxine hydrochloride 100 mg
Hydroxocobalamin hydrochloride 1.027 mg Tocopherol acetate 100 mg
Lactose 2700 mg Crystalline cellulose 300 mg Light anhydrous
silicic acid 5 mg Magnesium stearate 10 mg Cornstarch qs Total 4000
mg (2 g per container (powder paper), twice a day)
[0112] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was granulated to afford granules
in the same fashion as above.
Example 19
Capsules
[0113]
19 Curcumin 30 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Vitamin A oil 4 mg Cholecalciferol 0.005 mg Tocopherol
acetate 10 mg Vitamin C 600 mg Crystalline cellulose 250 mg
Magnesium stearate 6 mg Cornstarch qs Total 1150 mg (for 4 #1
capsules, 2 capsules per dose, twice a day)
[0114] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended and packed to afford
capsules in the same fashion as above.
Example 20
Capsules
[0115]
20 Curcumin 25 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Cephalexin 375 mg Cornstarch qs Magnesium stearate 6 mg
Total 855 mg (for 3 #2 capsules)
[0116] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended and packed to afford
capsules in the same fashion as above.
Example 21
Soft Capsules
[0117]
21 Curcumin 25 mg Sodium scymnol sulfate 1 mg Soybean isoflavone
125 mg Cod liver oil 80 mg Tocopherol acetate 5 mg Heptadecanoic
acid 30 mg Inosinic acid 100 mg Ginseng extract 200 mg Yellow
beeswax 55 mg Edible oil qs Total 1200 mg (4 capsules a day)
[0118] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended and packed to afford soft
capsules in the same fashion as above.
Example 22
Soft Capsules
[0119]
22 Curcumin 30 mg Cholic acid 60 mg Soybean isoflavone glycoside
125 mg Heptadecanoic acid 30 mg Inosinic acid 100 mg Yellow beeswax
55 mg Edible oil qs Total 1200 mg (4 capsules a day)
[0120] A formula except that soybean isoflavone glycoside was
replaced with soybean isoflavone was blended and packed to afford
soft capsules in the same fashion as above.
Example 23
Powders
[0121]
23 Scymnol 1 mg Soybean isoflavone 125 mg Lactose 800 mg Cornstarch
qs Magnesium stearate 10 mg Total 2000 mg (1 g per container
(powder paper), twice a day)
[0122] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended to afford powders in the
same fashion as above.
Example 24
Granules
[0123]
24 Sodium scymnol sulfate 1 mg Soybean isoflavone 125 mg Lactose
1500 mg Cornstarch qs Magnesium stearate 10 mg Total 2000 mg (1 g
per container (powder paper), twice a day)
[0124] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was granulated to afford granules in
the same fashion as above.
Example 25
Tablets
[0125]
25 Sodium scymnol sulfate 1 mg Soybean isoflavone 125 mg
Crystalline cellulose qs Lactose 140 mg Magnesium stearate 6 mg
Talc 3 mg Total 1120 mg (280 mg per tablet, 2 tablets per dose,
twice a day)
[0126] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was compressed to afford tablets in
the same fashion as above.
Example 26
Hard Capsules
[0127]
26 Scymnol 1 mg Soybean isoflavone 125 mg Lactose 218 mg Cornstarch
qs Magnesium stearate 6 mg Total 1150 mg (for 4 #1 capsules, 2
capsules per dose, twice a day)
[0128] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended and packed to afford hard
capsules in the same fashion as above.
Example 27
Soft Capsules
[0129]
27 Sodium scymnol sulfate 1 mg Soybean isoflavone 125 mg Cod liver
oil 80 mg Tocopherol acetate 5 mg Ginseng extract 200 mg Yellow
beeswax 55 mg Edible oil qs Total 1200 mg (4 capsules a day)
[0130] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was blended and packed to afford soft
capsules in the same fashion as above.
Example 28
Drink
[0131]
28 Sodium scymnol sulfate 1 mg Soybean isoflavone 125 mg Korean
ginseng extract 10 mg Rehmanniae Radix extract 10 mg Royal jelly
100 mg Thiamin nitrate 10 mg Riboflavin sodium phosphate 5 mg
Pyridoxine hydrochloride 10 mg Anhydrous caffeine 50 mg Ethanol 1.2
mL Ethyl parahydroxybenzoate 4 mg Purified water qs Total 50
mL/bottle
[0132] A formula except that soybean isoflavone was replaced with
soybean isoflavone glycoside was mixed to afford drinks in the same
fashion as above.
Example 29
Injectable Solution
[0133]
29 Sodium scymnol sulfate 1 mg Purified soybean isoflavone 20 mg
Glucose 500 mg
[0134] The pH is adjusted to 7 with 10% sodium hydroxide for pH
adjustment, distilled water for injection is added to make the
total amount 5 mL, and an ampoule filled therewith is sealed and
sterilized.
[0135] An injectable solution was produced in the same manner using
soybean isoflavone glycoside in lieu of soybean isoflavone.
Example 30
Nourishing Cream (O/W)
[0136]
30 (A) POE(40) monostearate 3.0 g Sorbitan monopalmitate 1.0 g
Cetyl isooctanoate 10.0 g Isopropyl myristate 5.0 g Liquid paraffin
(#70) 5.0 g MC stearic acid 10.0 g Cetanol 3.0 g Paraffin wax
(135.degree. F.) 3.0 g Dehydrated lanoline 2.0 g Pyridoxine
dipalmitate 0.3 g Methylparaben 0.1 g Butylparaben 0.1 g Cholic
acid 0.1 g Soybean isoflavone (on 100% purity basis) 0.5 q
Acetylgalactose 2.0 g Curcumin 0.1 g (B) Borax 0.5 g Propylene
glycol 5.0 g Purified water q.s. Total 100.0 g (C) Perfume 0.3 to
0.6 g
Example 31
Emulsions
[0137]
31 (A) POE(20) behenyl ether 2.4 g Sorbitan monopalmitate 1.6 g
Isostearyl palmitate 5.0 g Isopropyl myristate 3.0 g Dehydrated
lanoline 1.5 g MC stearic acid 1.0 g Cetanol 1.0 g Beeswax 2.0 g
Paraffin wax (135.degree. F.) 2.0 g Spermaceti 2.0 g Methylparaben
0.1 g Butylparaben 0.1 g Cholic acid 0.1 g Acetylgalactose 2.0 g
Curcumin 0.1 g (B) Borax 0.5 g Carbopol 940 (2% aqueous solution)
10.0 g Propylene glycol 10.0 g Soybean isoflavone (on 100% purity
basis) 0.1 g Galactose 2.0 g Purified water q.s. Total 100.0 g (C)
Perfume 0.2 to 0.4 g
Example 32
Nourishing Cream (W/O)
[0138]
32 (A) POE(15) glycerol vegetable oil fatty acid ester 1.5 g
Sorbitan sesquioleate 3.5 g Isopropyl myristate 10.0 g Liquid
paraffin (#70) 10.0 g Cetanol 4.0 g Paraffin wax (135.degree. F.)
5.0 g Beeswax 10.0 g Methylparaben 0.1 g Butylparaben 0.1 g Cholic
acid 0.5 g Acetylgalactose 2.0 g Curcumin 0.1 g (B) Borax 0.5 g
Propylene glycol 2.0 g Soybean isoflavone (on 100% basis) 1.0 g
Purified water q.s. Total 100.0 g (C) Perfume 0.3 to 0.5 g
Example 33
Cold Cream (W/O)
[0139]
33 (A) POE(6) sorbitan monooleate 1.0 g Sorbitan monoisostearate
4.0 g Batyl monoisostearate 1.0 g Liquid paraffin (#70) 25.0 g
Lanoline alcohol 4.0 g Beeswax 15.0 g Paraffin wax (135.degree. F.)
5.0 g Methylparaben 0.1 g Butylparaben 0.1 g Acetylgalactose 2.0 g
Soybean isoflavone (on 100% purity basis) 0.1 g Cholic acid 0.1 g
(B) Borax 0.8 g Purified water q.s. Total 100.0 g (C) Perfume 0.3
to 0.5 g
[0140] No studies have been conducted on the efficacy of curcumin,
zingerone, or shogaol on the stimulation of adrenaline secretion.
However, the secretomotory actions on adrenaline have been
clarified through animal experiments using mice in which blood
glucose levels were remarkably elevated.
[0141] Tablets of Example 4 were administered once a day.
[0142] For an eighty-three year old male afflicted with walking
difficulties and severe anal prolapse, occurred as he was aging,
the dosing led to easy mobility and recovery from proctoptosia,
with a clear feeling that the anal sphincter functioned. One-month
dosing led to clear amelioration of his conditions.
[0143] For a male (age 63) afflicted with difficulty in walking up
and down stairs, the dosing led to easy movement on staircases.
One-month dose trials led to clear amelioration. The tablet of
example 13 has a similar efficacy.
[0144] If these results were simply attributable to pharmacological
action to improve local muscle activity, such information would be
contained in European and American data and in results found in
Okinawa, wherein curcumin is applied. No such data exists therein.
This indicates that these results might be attributed to
improvements in brain communication of commands (released as a
result of brain thought) to local sites.
[0145] In Western medicine, it has been understood that
proctoptosia and leg, lumbus and arm aches are attributable only to
hematogenous disorders and resultant inflammation at local sites.
However, these pathological conditions were not significantly
ameliorated by a single regular dose of drugs admixed with one of
scymnol, isoflavone, and cholic acid which are significantly
capable of removing hematogenous disorders. Thus, it can be
understood that these disorders are attributed to insufficient
communication of brain commands to local sites and therefore the
hematogenous disorders and onset of inflammation are problems
caused by abnormal motions of muscles due to incomplete
communication of brain commands.
[0146] When male and female patients (5 each, age 60 to 75)
complained of backaches, limb pains and muscle disorders such as
proctoptosia (which occurred as they were aging) took doses, such
clinical conditions were alleviated or cured.
[0147] Although all muscle disorders are not ascribable to
insufficient brain communication, it seems that the majority of
such disorders are elicited by insufficient communication of brain
commands.
[0148] Coadministration of isoflavone, cholic acid, scymnol,
curcumin and so on enables the removal of muscle disorders as such
components have the stimulating actions on brain activity. This is
good news to the elders for both physical and mental rejuvenation.
These formulations are extremely effective for arthritis such as
rheumatism and in particular, greatly influence the prevention.
[0149] Curcumin is readily available. For instance, highly pure
curcumin is on the market.
[0150] Capsaicine (30 mg) instead of curcumin preparations of
Example 1 was administered to elderly patients between the ages of
76 and 83 once daily. Several days later, its effects were
dramatic. It has been proved that the drug is effective for
muscular degeneration, arthritis and rheumatism after one week.
Capsaicine is a powerful irritant with burning aftertaste.
[0151] Administration of the agent or composition of Example 6
produced the following effects.
[0152] When the drug was administered to a 74-year-old female, her
lumbargo was cured in 6 weeks. After the inventive drug was
administered to a 39-year-old woman for 6 weeks, her headache
vanished. In a 56-year-old woman, one week administration resulted
in recovery from her rheumaotid arthritis. When it was administered
to a 70-year-old woman, her arthralgia and pain in osteomere
disappeared in 2 weeks. After the drug was administered to a
59-year-old woman for 6 weeks, her painful stiffness in neck and
shoulder was obviated.
[0153] The capsule of Example 6 was given once daily, producing the
following effects.
[0154] In a 39-year-old woman complaining of cold feeling, headache
and diminution of vision, such symptoms disappeared after the drug
was administered for 6 weeks. In a 53-year-old woman with
arrhythmia, a marked relief was attained after the pharmaceutical
preparation was administered for 1 year. In a 71-year-old man with
sequela following cerebral infarction and with motor paralysis in
the left side of the body, the treated conditions were alleviated
after the pharmaceutical preparation was administered for 8 weeks.
In a 66-year-old woman with sequela following cerebral infarction
and with motor paralysis in the left side of the body, the
conditions were markedly ameliorated after the pharmaceutical
preparation was administered for 8 weeks. In a 73-year-old woman
with sequela following cerebral infarction and with motor paralysis
in the left side of the body, the treated conditions were markedly
ameliorated after the pharmaceutical preparation was administered
for 8 weeks, In a 43-year-old woman with paroxysmal positional
nystagmus, the conditions were alleviated after the pharmaceutical
preparation was administered for 6 weeks. In a 64-year-old woman
with asthma, the symptoms were significantly ameliorated after the
pharmaceutical preparation was administered for 4 weeks.
[0155] In a 25-year-old man with irritable colitis, the treated
condition was cured after the drug was administered for 4 weeks. In
a 32-year-old man with irritable colitis, the condition was
ameliorated after administration over 4 weeks. In a 66-year-old man
with gastric ulcer and diarrhea, the treated conditions were cured
after administration for 2 weeks. In a 66-year-old woman with
diarrhea, the treated condition was cured after administration for
4 weeks. In a 29-year-old woman with ulcerative colitis, the
disease was cured after administration for 1 week. In a 42-year-old
woman with diarrhea and feeling of cold, the conditions were cured
after administration for 8 weeks. In a man with repeated diarrhea
and constipation, the symptoms were cured. In a 36-year-old man
with Crohn disease, the disease was cured after administration for
3 weeks. When the drug was administered to a 48-year-old man with
hepatitis for 2 weeks, the disease was cured. In a 48-year-old
woman with chromic nephritis, the diseases were markedly alleviated
after administration for 6 weeks.
[0156] In a 64-year-old woman with hypothyroidism, the treated
condition was ameliorated after administration over 16 weeks. In a
39-year-old woman with feeling of cold, fatigability, headache and
diminution of vision, the conditions were cured after
administration for 6 weeks. In a 74-year-old woman with lumbargo,
abdominal pain and amnesia, the treated conditions were ameliorated
after administration for 6 weeks. In a 60-year-old woman with
edema, lumbargo and pain in the knee, the diseases were markedly
alleviated after administration for 12 weeks. In a 39-year-old
woman with feeling of cold and fatigability, the symptoms were
obviated after administration for 6 weeks. In a 71-year-old woman
with vertigo and tinnitus, the diseases were alleviated in 6 weeks.
In a 41-year-old woman with chromic fatigue, the symptom was
alleviated after administration for 6 weeks. In a 54-year-old woman
with chronic fatigue syndrome, the conditions were alleviated after
administration for 17 weeks. In a 47-year-old man with chronic
fatigue, the treated condition was relieved after administration
for 6 weeks. In a 72-year-old man in a subvirile condition, the
treated symptom was cured after the preparation was administered
for 8 weeks. In a 71-year-old woman with tinnitus and feeling of
fatigue, the conditions were ameliorated after the preparation was
administered for 9 weeks. In a 43-year-old woman with paroxysmal
positional nystagmus, the symptom was ameliorated after the
preparation was administered for 6 weeks. In a 54-year-old woman
with chronic fatigue syndrome, the conditions were alleviated after
the preparation was administered for 17 weeks. After administration
over a period of 16 weeks, a relief was achieved in a 50-year-old
man complaining of weariness and enervation. In a 75-year-old woman
(an atomic bomb victim) with lung cancer and senile dementia, the
conditions were relieved and the side effects of drugs for lung
cancer and atomic bomb syndrome were alleviated after the
preparation was administered for 4 weeks. In a 36-year-old woman
complaining of enervation and physical weakness, the conditions
were ameliorated after administration for 12 weeks. In a
71-year-old man with senile dementia, the disease was cured after
the preparation was administered for 9 weeks. In a 75-year-old
woman with senile dementia, the disease was alleviated after
administration for 4 weeks. In a 60-year-old woman with lacunar
dementia, the treated condition was cured after the preparation was
administered for 12 weeks.
[0157] In a 34-year-old woman with lung cancer and brain tumor, the
treated conditions were alleviated significantly after the
preparation was administered for 4 weeks. In a 51-year-old woman
with breast cancer and lymphoma, the treated conditions were
alleviated remarkably after administration over a period of 2
weeks.
[0158] After the capsule preparation of Example 6 was administered
over a period of 16 weeks, the following effects were produced as
for hair, for instance.
[0159] In a 62-year-old silver-haired man, black hair grew along
the hairline. In a 61-year-old man, the sideburns and the hair in
the middle of forehead became black. In a 55-year-old man, two
black hairs grew in the forehead. In a 68-year-old woman, black
hair grew along the forehead line, and the hair on the forearm
became abnormally long. The hair growth phenomenon was remarkable
in the left side of the body. In a 68-year-old woman, the hair
became black like a wig along the forehead line. In an 82-year-old
woman, her eyebrows became thick. In a 55-year-old man, 9 to 12
black hairs grew along his receding forehead line. In a 64-year-old
woman, hair grew and her verrucae disappeared. In a 74-year-old
woman, her eyebrows became black. In a 64-year-old woman with
hypothyroidism and alopecia, the treated conditions were cured
after the preparation was administered for 16 weeks. When a
74-year-old healthy woman receive the preparation for 16 weeks, her
alopecia was cured by the administration. In a 34-year-old woman
with lung cancer and brain tumor, a marked relief was produced with
respect to alopecia due to adverse effects of cancer therapy. In a
69-year-old woman with vitiligo, the skin became reddened after the
preparation was administered for 2 weeks. In a 55-year-old woman
with vitiligo, a relief was brought about after administration for
4 weeks.
[0160] Similarly, it has also been verified that the instant
products have skin beautifying actions and pharmacological actions
such as therapeutic or prophylactic actions against atopic
dermatitis, various types of dermatitis, dermatomycosis,
verrucosis, pigmentation, vulgar psoriasis, senile xeroderma,
senile keratoma, and skin injuries, and hair-restoring, peptic
juice secretion promoting, perspiration promoting, lapactic,
diuretic and other actions.
[0161] Tablets (250 mg each) containing curcumin (15 mg), cholic
acid (20 mg) and soybean isoflavone glycoside (40 mg) in admixture
with lactose were administered at a dose of 3 tablets a day (at a
dose of 45 mg of curcumin once a day) to 10 patients who had
regularly received drugs having the efficacy of "FU-SEI" (in
Japanese). The results are shown in the following Table:
34 TABLE 1 Drug Regularly Dosed Age Sex Pathological State
Antidepressant Tranquilizer Hypnotic Hospitalization Efficacy 1 51
Male Severe Depression, Anxiety .largecircle. .largecircle.
.largecircle. .largecircle. .circleincircle. 2 38 Male Insomnia,
Anxiety, Irritableness .largecircle. .largecircle. .largecircle.
.largecircle. .largecircle. 3 51 Male Insomnia, Anxiety X X X X --
4 30 Female Insomnia. Anxiety, Depression .largecircle.
.largecircle. .largecircle. X .circleincircle. 5 18 Female
Insomnia, Anxiety, Irritableness X X X X .circleincircle. 6 76 Male
Irritableness X X X X .largecircle. 7 74 Female Intensive Anxiety,
Insomnia, X X X X .largecircle. Irritableness 8 48 Female
Depression, Excessive sleeping .largecircle. .largecircle. X X
.circleincircle. 9 48 Male Psychomotor detardation, X X X X
.circleincircle. Irritableness, Intensive Depression 10 39 Female
Intensive Depression, Insomnia, X X X X .circleincircle. Anxiety
All patients were diagnosed as suffering from depression by
specialized physicians. For efficacy: .largecircle., effective;
.circleincircle., significantly effective; --, follow-up
[0162] As shown in the above Table, the drug is effective in 90% of
the cases and the significantly effective case equals 60%.
[0163] These good results indicate the possibility of recovery from
depression which had been said to be a non-curable disease. The
examples as disclosed in the Table show results obtained from
dosage trials over two months after the initiation of
administration; however, long term observation is required for
recurrence of depression. Thus, it has been proven that many
curcumin-dosed patients are able to return to daily life routines
nearly identical to those of ordinary people (non-sufferers of
depression), demonstrating that these antidepressants of the
present invention are extremely effective in treating
depression.
[0164] When tablets (250 mg each) containing, in admixture with
lactose, sodium scymnol sulfate (1 mg) in place of cholic acid were
administered, similar results were obtained.
[0165] Similarly, granules of Examples 2 and 11 were administered
to 12 and 14 females with menopausal disorders including
broodiness, depression and dizziness, etc., respectively, at 45 mg
of curcumin per day. Five days after the dosing, the broodiness,
depression and dizziness were mitigated in five and six
individuals, respectively. Three weeks later, improvements were
seen in 11 and 12 individuals, respectively.
[0166] When the preparation was administered to 10 forgetful
patients just in a preliminary step of senile dementia, the
forgetfulness was alleviated in 7 patients. The preparation was
also useful in the treatment of Alzheimer disease.
[0167] When granules of Example 2 were administered to 10 elderly
patients in the preliminary stages of senile dementia, memory loss
was ameliorated in 7 individuals. When granules of Example 11 were
administered, similar results were obtained. Such products are also
effective for Alzheimer's disease.
[0168] After the preparation of Example 7 was administered to a
51-year-old man with a tendency toward depression, weariness and
enervation over a period of 16 weeks, the treated states were
alleviated. In a 38-year-old woman with autonomic nervous system
excitement, enervation and poor physical strength, the treated
conditions were alleviated after administration for 2 weeks. After
the preparation was administered to a 59-year-old woman with sever
emaciation following hysterectomy for 6 weeks, the treated
conditions were alleviated significantly. After the preparation was
administered to a 46-year-old woman with anemia and hemorrhoid, for
8 weeks, the treated symptoms were remarkably alleviated. When the
inventive preparation was administered to a 71-year-old man with
sequela of cerebral infarction and with senile dementia for 10
weeks, the treated conditions were significantly relieved.
[0169] Curcumin is readily available. For instance, highly pure
curcumin is on the market.
[0170] Capsules wherein powders produced by admixture of capsaicine
(50 mg) with lactose were packed in combination with isoflavone
glycoside and cholic acid were administered to patients with
depression once daily. Several days later, effects were dramatic.
The patient were nearly completely recovered from depression after
a week. Capsaicine is a powerful irritant with burning
aftertaste.
ADVANTAGES OF THE PRESENT INVENTION
[0171] The present invention is very effective and advantageous in
that it can provide pharmaceutical agents or compositions useful as
muscle-strengthening drugs, anti-inflammatory drugs,
antiasthmatics, antidiarrheals, antidepressants, or drugs for the
treatment of secondary diseases following cerebral infarction,
motor paralysis, diminution of vision, hepatitis, inflammatory
intestinal syndrome, functional enteropathy, functional
cardiopathy, functional hepatopathy, functional nephropathy,
dementia, climacteric symptoms, senile dementia and/or Alzheimer
disease, and dermatological agents or compositions suitable for
skin applications, which can treat or prevent muscle weakening and
inflammation, in particular arthritis and rheumatism, by the
synergistic action resulting from administration of isoflavone,
cholic acid or scymnol, and a pungent, bitter or sour substance, in
particular a pungent substance.
[0172] When used as an agent for skin use, the composition can
produce good cosmetic effects such as whitening, blotch-removing,
wrinkle-removing, trichogenous and/or hair-restoring effects, as
well as skin beautifying effects and pharmacological effects such
as therapeutic effects against atopic dermatitis, various types of
dermatitis, dermatomycosis, verrucosis, pigmentation, vulgar
psoriasis, senile xeroderma, senile keratoma, and skin injuries,
and hair-restoring, peptic juice secretion promoting, perspiration
promoting, lapactic, diuretic and other effects.
[0173] The agent or composition is also advantageously effective in
preventing adverse effects of anticancer drugs, namely depilation,
internal hemorrhage, diarrhea, and disorders of heart, liver,
kidney, etc. Therefore, when used in combination with an anticancer
drug, it can suppress those side effects otherwise produced by such
drugs.
* * * * *